It is a long time since image diagnosis with X-ray CT, MRI (magnetic resonance imaging), ultrasonography, etc. became an essential tool in medical practice. These technologies produce images due to CT values, spin relaxation time, acoustic impedance, etc. varying from one living tissue to another. Imaging by them is called “anatomical imaging” because their physical values depend solely on the anatomic properties of the living body. By contrast, there is another type of imaging called “functional imaging”, which is designed to examine tissues which are identical in structure but different in function. It is sometimes called “molecular imaging” when it is used to elucidate the structure of molecules (such as proteins) constituting a living body.
Molecular imaging is one of the research areas most attracting attention because of its potential application to elucidation of life phenomenon (such as development and differentiation) and diagnosis and therapy of diseases. Molecular imaging usually employs a “molecular probe” which is a substance with structural selectivity for molecules constituting a living body. It is given something that visualizes its distribution in a living body. An example of a molecular probe to target a tumor is disclosed in Non-Patent Document 1. Major molecular probes are peptides and proteins such as antibodies.
A molecular probe in a living body is visualized on the image diagnostic equipment when it chemically or physically combines with a substance called contrast agent or reporter that modifies its structure. The term “contrast agent” usually denotes a substance used to diagnose the blood flow. It is generally used in ultrasonography. A prevailing ultrasound contrast agent is minute bubbles with a diameter of the order of micrometers. Ultrasonography visualizes substances that vary in acoustic impedance (product of density and sound velocity) from one place to another. It easily visualizes air bubbles in a living body which have a much smaller acoustic impedance than tissues constituting a living body (ca. 0.004×106 kg/m2·s vs. ca. 1.5×106 kg/m2·s). Moreover, it selectively visualizes signals from minute air bubbles of the order of micrometers which resonate with diagnostic ultrasound of high-frequencies in the MHz band and generate higher harmonics from the impingent ultrasound. This leads to highly sensitive imaging.
One conceivable way of realizing molecular imaging with ultrasound is to employ an ultrasound contrast agent composed of bubbles and molecular probes which is in use for diagnosis of blood flow as mentioned above. In fact, such a ultrasound contrast agent responsive to thrombi has been developed, as disclosed in Patent Document 1. Another type of ultrasound contrast agent responsive to new blood vessel is also under study, as disclosed in Non-Patent Document 2. As disclosed in Non-Patent Document 3, it is a liquid differing in acoustic impedance from a living body which is enclosed in microcapsules of submicron size capable of migrating from blood vessels into tissues.
Another ultrasound contrast agent having all the merits of earlier ones is disclosed in Patent Document 2. It is a liquid compound in the form of fine particles divided by a surfactant, which is vaporized by ultrasound in a living body after administration. This type of ultrasound contrast agent will permit highly sensitive imaging by resonance because it is not limited in retention time in a living body and parts to which it is applied and because it keeps a gas phase during imaging operation.    Patent Document 1:
U.S. Pat. No. 6,521,211    Patent Document 2:
U.S. Pat. No. 5,716,597    Non-Patent Document 1:
Allen, Nature Rev. Cancer, 2, 750-763 (2002)    Non-Patent Document 2:
Ellegala et al., Circulation, 108, 336-341 (2003)    Non-Patent Document 3:
Lanza et al., Circulation, 94, 3334-3340 (1996)    Non-Patent Document 4:
Umemura et al., Prc. IEEE Ultrasonics Symposium, 2, 1311-1314 (2001)